Pathophysiology of Red Blood Cell Dysfunction in Diabetes and Its Complications

Abstract

Diabetes Mellitus (DM) is a complex metabolic disorder associated with multiple microvascular complications leading to nephropathy, retinopathy, and neuropathy. Mounting evidence suggests that red blood cell (RBC) alterations are both a cause and consequence of disturbances related to DM-associated complications. Importantly, a significant proportion of DM patients develop varying degrees of anemia of confounding etiology, leading to increased morbidity. In chronic hyperglycemia, RBCs display morphological, enzymatic, and biophysical changes, which in turn prime them for swift phagocytic clearance from circulation. A multitude of endogenous factors, such as oxidative and dicarbonyl stress, uremic toxins, extracellular hypertonicity, sorbitol accumulation, and deranged nitric oxide metabolism, have been implicated in pathological RBC changes in DM. This review collates clinical laboratory findings of changes in hematology indices in DM patients and discusses recent reports on the putative mechanisms underpinning shortened RBC survival and disturbed cell membrane architecture within the diabetic milieu. Specifically, RBC cell death signaling, RBC metabolism, procoagulant RBC phenotype, RBC-triggered endothelial cell dysfunction, and changes in RBC deformability and aggregation in the context of DM are discussed. Understanding the mechanisms of RBC alterations in DM provides valuable insights into the clinical significance of the crosstalk between RBCs and microangiopathy in DM.

Task-Oriented Predictive (Top)-BERT: Novel Approach for Predicting Diabetic Complications Using a Single-Center EHR Data

“…Low serum magnesium is linked to key diabetes complications, including retinopathy and heart disease, while polypharmacy can lead to hypopotassemia, further increasing cardiovascular risk. Our findings also showed association of vitamin D with both micro and macro-vascular complications, as well as identified anemia a significant predictive factor, corroborating existing clinical evidence 51, 52 .…”

Evaluating the biological (antidiabetic) potential of TEM, FTIR, XRD, and UV‐spectra observed berberis lyceum conjugated silver nanoparticles

“…The rigidity of plasma membrane could be increased due to free radicals-induced lipid peroxidation of the membrane and lessened deformability of cells; reduced survival of erythrocytic and lipids fluidity (Kolanjiappan et al, 2002). Hemoglobin (Hb) values in diabetic mice displayed noteworthy reduction by preceding hematological studies reporting anemia as a pathophysiological complication of DM (Williams et al, 2023). Abnormal synthesis of Hb and blood osmoregulation defect could be the cause of this reduction (Dubey et al, 2023).…”

Red blood cells as biomarkers and mediators in complications of diabetes mellitus: A review

“…[18] Reduced blood flow and microvascular changes in the retina are key factors in the development of diabetic retinopathy, a leading cause of vision impairment and blindness. [19,20] Dysfunctional RBCs may contribute to renal microvascular damage and impairments in kidney function. Altered blood flow and reduced oxygen delivery to the kidneys are associated with the development of diabetic nephropathy, a major cause of end-stage renal disease.…”

“…[8] Certainly, in diabetic conditions, RBCs undergo various alterations in their structure, function, and lifespan due to the complex interplay of factors associated with hyperglycemia and its sequelae. [9] Chronic exposure to high levels of glucose in the bloodstream leads to the non-enzymatic glycated hemoglobin (HbA1c) molecules within RBCs. This process results in the formation of HbA1c, which reflects the average blood glucose levels over a prolonged period.…”